NEUR2_HUMAN
ID NEUR2_HUMAN Reviewed; 380 AA.
AC Q9Y3R4; Q3KNW4; Q6NTB4;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Sialidase-2;
DE EC=3.2.1.18 {ECO:0000269|PubMed:14613940, ECO:0000269|PubMed:22228546};
DE AltName: Full=Cytosolic sialidase;
DE AltName: Full=N-acetyl-alpha-neuraminidase 2;
GN Name=NEU2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND VARIANT ASN-168.
RX PubMed=10191093; DOI=10.1006/geno.1999.5749;
RA Monti E., Preti A., Rossi E., Ballabio A., Borsani G.;
RT "Cloning and characterization of NEU2, a human gene homologous to rodent
RT soluble sialidases.";
RL Genomics 57:137-143(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-168.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=10561456; DOI=10.1093/glycob/9.12.1313;
RA Monti E., Preti A., Nesti C., Ballabio A., Borsani G.;
RT "Expression of a novel human sialidase encoded by the NEU2 gene.";
RL Glycobiology 9:1313-1321(1999).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
RP SPECIFICITY.
RX PubMed=14613940; DOI=10.1074/jbc.m308381200;
RA Tringali C., Papini N., Fusi P., Croci G., Borsani G., Preti A.,
RA Tortora P., Tettamanti G., Venerando B., Monti E.;
RT "Properties of recombinant human cytosolic sialidase HsNEU2. The enzyme
RT hydrolyzes monomerically dispersed GM1 ganglioside molecules.";
RL J. Biol. Chem. 279:3169-3179(2004).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF ASP-46;
RP GLU-218 AND GLN-270.
RX PubMed=22228546; DOI=10.1002/prot.24013;
RA Mozzi A., Mazzacuva P., Zampella G., Forcella M.E., Fusi P.A., Monti E.;
RT "Molecular insight into substrate recognition by human cytosolic sialidase
RT NEU2.";
RL Proteins 80:1123-1132(2012).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.49 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR
RP 2-DEOXY-2,3-DEHYDRO-N-ACETYLNEURAMINIC ACID.
RX PubMed=15501818; DOI=10.1074/jbc.m411506200;
RA Chavas L.M.G., Tringali C., Fusi P., Venerando B., Tettamanti G., Kato R.,
RA Monti E., Wakatsuki S.;
RT "Crystal structure of the human cytosolic sialidase Neu2. Evidence for the
RT dynamic nature of substrate recognition.";
RL J. Biol. Chem. 280:469-475(2005).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG,
RP AND ACTIVE SITE.
RA Buchini S., Gallat F.X., Greig I.R., Kim J.H., Wakatsuki S., Withers S.G.;
RT "Tuning mechanism-based inactivators of neuraminidases: mechanistic and
RT structural insights.";
RL Submitted (NOV-2013) to the PDB data bank.
RN [10]
RP CHARACTERIZATION OF VARIANT GLN-41.
RX PubMed=17426694; DOI=10.1038/cr.2007.27;
RA Li C.-Y., Yu Q., Ye Z.-Q., Sun Y., He Q., Li X.-M., Zhang W., Luo J.,
RA Gu X., Zheng X., Wei L.;
RT "A nonsynonymous SNP in human cytosolic sialidase in a small Asian
RT population results in reduced enzyme activity: potential link with severe
RT adverse reactions to oseltamivir.";
RL Cell Res. 17:357-362(2007).
CC -!- FUNCTION: Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of
CC the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan
CC moiety in the catabolism of glycolipids, glycoproteins and
CC oligosacharides (PubMed:14613940, PubMed:22228546). Recognizes sialyl
CC linkage positions of the glycan moiety as well as the supramolecular
CC organization of the sialoglycoconjugate. Displays preference for alpha-
CC (2->3)-sialylated GD1a and GT1B gangliosides over alpha-(2->8)-
CC sialylated GD1b, in both monomeric forms and micelles. Hydrolyzes
CC monomeric GM1 ganglioside, but has no activity toward the miscellar
CC form (PubMed:14613940). Has lower sialidase activity for glycoproteins
CC such as fetuin and TF/transferrin that carry a mixture of alpha-(2->3)
CC and alpha-(2->6)-sialyl linkages. Cleaves milk oligosaccharide alpha-
CC (2->3)-sialyllactose, but is inactive toward alpha-(2->6)-sialyllactose
CC isomer. Has no activity toward colominic acid, a homomer of alpha-
CC (2->8)-linked Neu5Ac residues (PubMed:14613940).
CC {ECO:0000269|PubMed:14613940, ECO:0000269|PubMed:22228546}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-
CC (2->8)- glycosidic linkages of terminal sialic acid residues in
CC oligosaccharides, glycoproteins, glycolipids, colominic acid and
CC synthetic substrates.; EC=3.2.1.18;
CC Evidence={ECO:0000269|PubMed:14613940, ECO:0000269|PubMed:22228546};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GD1a + H2O = ganglioside GM1 + N-
CC acetylneuraminate; Xref=Rhea:RHEA:47832, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:35418, ChEBI:CHEBI:82637, ChEBI:CHEBI:82639;
CC Evidence={ECO:0000269|PubMed:14613940};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47833;
CC Evidence={ECO:0000305|PubMed:14613940};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GM1 + H2O = ganglioside GA1 + N-acetylneuraminate;
CC Xref=Rhea:RHEA:47872, ChEBI:CHEBI:15377, ChEBI:CHEBI:35418,
CC ChEBI:CHEBI:82639, ChEBI:CHEBI:88069;
CC Evidence={ECO:0000269|PubMed:14613940};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47873;
CC Evidence={ECO:0000305|PubMed:14613940};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GT1b + H2O = ganglioside GD1b + N-
CC acetylneuraminate; Xref=Rhea:RHEA:47828, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:35418, ChEBI:CHEBI:82939, ChEBI:CHEBI:82940;
CC Evidence={ECO:0000269|PubMed:14613940};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47829;
CC Evidence={ECO:0000305|PubMed:14613940};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GD1b + H2O = ganglioside GM1 + N-
CC acetylneuraminate; Xref=Rhea:RHEA:47876, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:35418, ChEBI:CHEBI:82639, ChEBI:CHEBI:82939;
CC Evidence={ECO:0000269|PubMed:14613940};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47877;
CC Evidence={ECO:0000305|PubMed:14613940};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GD3 + H2O = ganglioside GM3 + N-acetylneuraminate;
CC Xref=Rhea:RHEA:48120, ChEBI:CHEBI:15377, ChEBI:CHEBI:35418,
CC ChEBI:CHEBI:79210, ChEBI:CHEBI:79214;
CC Evidence={ECO:0000250|UniProtKB:Q9JMH3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48121;
CC Evidence={ECO:0000250|UniProtKB:Q9JMH3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GM3 + H2O = beta-D-galactosyl-(1->4)-beta-D-
CC glucosyl-(1<->1)-ceramide + N-acetylneuraminate;
CC Xref=Rhea:RHEA:48136, ChEBI:CHEBI:15377, ChEBI:CHEBI:35418,
CC ChEBI:CHEBI:79208, ChEBI:CHEBI:79210;
CC Evidence={ECO:0000269|PubMed:14613940, ECO:0000269|PubMed:22228546};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48137;
CC Evidence={ECO:0000305|PubMed:14613940, ECO:0000305|PubMed:22228546};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GM2 + H2O = N-acetyl-beta-D-galactosaminyl-(1->4)-
CC beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1')-ceramide + N-
CC acetylneuraminate; Xref=Rhea:RHEA:48172, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:35418, ChEBI:CHEBI:79218, ChEBI:CHEBI:90085;
CC Evidence={ECO:0000250|UniProtKB:Q9JMH3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48173;
CC Evidence={ECO:0000250|UniProtKB:Q9JMH3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a neolactoside IV(3)-alpha-NeuAc-nLc4Cer(d18:1(4E)) + H2O = a
CC neolactoside nLc4Cer(d18:1(4E)) + N-acetylneuraminate;
CC Xref=Rhea:RHEA:47852, ChEBI:CHEBI:15377, ChEBI:CHEBI:17006,
CC ChEBI:CHEBI:35418, ChEBI:CHEBI:58665;
CC Evidence={ECO:0000269|PubMed:14613940};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47853;
CC Evidence={ECO:0000305|PubMed:14613940};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-
CC (1->4)-D-glucose = lactose + N-acetylneuraminate;
CC Xref=Rhea:RHEA:64640, ChEBI:CHEBI:15377, ChEBI:CHEBI:17716,
CC ChEBI:CHEBI:35418, ChEBI:CHEBI:156068;
CC Evidence={ECO:0000269|PubMed:14613940, ECO:0000269|PubMed:22228546};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64641;
CC Evidence={ECO:0000305|PubMed:14613940, ECO:0000305|PubMed:22228546};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.24 mM for ganglioside GM3 (in the presence of Triton X-100)
CC {ECO:0000269|PubMed:14613940};
CC KM=0.14 mM for ganglioside GD1a (in the presence of Triton X-100)
CC {ECO:0000269|PubMed:14613940};
CC KM=0.51 mM for ganglioside GD1b (in the presence of Triton X-100)
CC {ECO:0000269|PubMed:14613940};
CC KM=0.38 mM for ganglioside GT1b (in the presence of Triton X-100)
CC {ECO:0000269|PubMed:14613940};
CC KM=0.28 mM for neolactoside IV(3)-alpha-NeuAc-nLc4Cer(d18:1(4E)) (in
CC the presence of Triton X-100) {ECO:0000269|PubMed:14613940};
CC KM=0.31 mM for alpha(2->3)-sialyllactose
CC {ECO:0000269|PubMed:14613940};
CC Vmax=67 umol/min/mg enzyme toward ganglioside GM3 (in the presence of
CC Triton X-100) {ECO:0000269|PubMed:14613940};
CC Vmax=322 umol/min/mg enzyme toward ganglioside GD1a (in the presence
CC of Triton X-100) {ECO:0000269|PubMed:14613940};
CC Vmax=5.45 umol/min/mg enzyme toward ganglioside GD1b (in the presence
CC of Triton X-100) {ECO:0000269|PubMed:14613940};
CC Vmax=190 umol/min/mg enzyme toward ganglioside GT1b (in the presence
CC of Triton X-100) {ECO:0000269|PubMed:14613940};
CC Vmax=253 umol/min/mg enzyme toward ganglioside neolactoside IV(3)-
CC alpha-NeuAc-nLc4Cer(d18:1(4E)) (in the presence of Triton X-100)
CC {ECO:0000269|PubMed:14613940};
CC Vmax=10 umol/min/mg enzyme toward alpha(2->3)-sialyllactose
CC {ECO:0000269|PubMed:14613940};
CC Vmax=12.7 umol/min/mg enzyme toward fetuin
CC {ECO:0000269|PubMed:14613940};
CC Vmax=0.75 umol/min/mg enzyme toward TF/transferrin
CC {ECO:0000269|PubMed:14613940};
CC Vmax=0.70 umol/min/mg enzyme toward alpha-1-acid glycoprotein
CC {ECO:0000269|PubMed:14613940};
CC pH dependence:
CC Optimum pH is 5.6. {ECO:0000269|PubMed:14613940};
CC -!- INTERACTION:
CC Q9Y3R4; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-10327976, EBI-3867333;
CC Q9Y3R4; Q7Z3S9: NOTCH2NLA; NbExp=6; IntAct=EBI-10327976, EBI-945833;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10561456}.
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle, fetal liver and
CC embryonic carcinoma cell line NT2-D1. {ECO:0000269|PubMed:10191093}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 33 family. {ECO:0000305}.
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DR EMBL; Y16535; CAB41449.1; -; Genomic_DNA.
DR EMBL; AC106876; AAY24360.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW71028.1; -; Genomic_DNA.
DR EMBL; BC069151; AAH69151.1; -; mRNA.
DR EMBL; BC107053; AAI07054.1; -; mRNA.
DR CCDS; CCDS2501.1; -.
DR RefSeq; NP_005374.2; NM_005383.2.
DR PDB; 1SNT; X-ray; 1.75 A; A=1-380.
DR PDB; 1SO7; X-ray; 1.49 A; A=1-380.
DR PDB; 1VCU; X-ray; 2.85 A; A/B=1-380.
DR PDB; 2F0Z; X-ray; 2.80 A; A=1-380.
DR PDB; 2F10; X-ray; 2.90 A; A=1-380.
DR PDB; 2F11; X-ray; 2.57 A; A=1-380.
DR PDB; 2F12; X-ray; 2.27 A; A=1-380.
DR PDB; 2F13; X-ray; 2.26 A; A=1-380.
DR PDB; 2F24; X-ray; 1.76 A; A=1-380.
DR PDB; 2F25; X-ray; 1.95 A; A/B=1-380.
DR PDB; 2F26; X-ray; 1.58 A; A=1-380.
DR PDB; 2F27; X-ray; 2.15 A; A/B=1-380.
DR PDB; 2F28; X-ray; 1.67 A; A=1-380.
DR PDB; 2F29; X-ray; 2.92 A; A/B=1-380.
DR PDB; 4NC5; X-ray; 2.51 A; A=1-380.
DR PDB; 4NCS; X-ray; 2.20 A; A=1-380.
DR PDBsum; 1SNT; -.
DR PDBsum; 1SO7; -.
DR PDBsum; 1VCU; -.
DR PDBsum; 2F0Z; -.
DR PDBsum; 2F10; -.
DR PDBsum; 2F11; -.
DR PDBsum; 2F12; -.
DR PDBsum; 2F13; -.
DR PDBsum; 2F24; -.
DR PDBsum; 2F25; -.
DR PDBsum; 2F26; -.
DR PDBsum; 2F27; -.
DR PDBsum; 2F28; -.
DR PDBsum; 2F29; -.
DR PDBsum; 4NC5; -.
DR PDBsum; 4NCS; -.
DR AlphaFoldDB; Q9Y3R4; -.
DR SMR; Q9Y3R4; -.
DR BioGRID; 110832; 64.
DR IntAct; Q9Y3R4; 22.
DR STRING; 9606.ENSP00000233840; -.
DR BindingDB; Q9Y3R4; -.
DR ChEMBL; CHEMBL3200; -.
DR DrugBank; DB03991; 2-deoxy-2,3-dehydro-N-acetylneuraminic acid.
DR DrugBank; DB07960; 5-ACETAMIDO-5,6-DIHYDRO-4-HYDROXY-6-ISOBUTOXY-4H-PYRAN-2-CARBOXYLIC ACID.
DR DrugBank; DB00198; Oseltamivir.
DR DrugBank; DB00558; Zanamivir.
DR DrugCentral; Q9Y3R4; -.
DR SwissLipids; SLP:000001360; -.
DR CAZy; GH33; Glycoside Hydrolase Family 33.
DR iPTMnet; Q9Y3R4; -.
DR PhosphoSitePlus; Q9Y3R4; -.
DR BioMuta; NEU2; -.
DR DMDM; 229462907; -.
DR MassIVE; Q9Y3R4; -.
DR PaxDb; Q9Y3R4; -.
DR PeptideAtlas; Q9Y3R4; -.
DR PRIDE; Q9Y3R4; -.
DR ProteomicsDB; 86068; -.
DR Antibodypedia; 34447; 270 antibodies from 27 providers.
DR DNASU; 4759; -.
DR Ensembl; ENST00000233840.3; ENSP00000233840.3; ENSG00000115488.3.
DR GeneID; 4759; -.
DR KEGG; hsa:4759; -.
DR MANE-Select; ENST00000233840.3; ENSP00000233840.3; NM_005383.2; NP_005374.2.
DR UCSC; uc010zmn.2; human.
DR CTD; 4759; -.
DR DisGeNET; 4759; -.
DR GeneCards; NEU2; -.
DR HGNC; HGNC:7759; NEU2.
DR HPA; ENSG00000115488; Tissue enriched (skin).
DR MIM; 605528; gene.
DR neXtProt; NX_Q9Y3R4; -.
DR OpenTargets; ENSG00000115488; -.
DR PharmGKB; PA31561; -.
DR VEuPathDB; HostDB:ENSG00000115488; -.
DR eggNOG; ENOG502QSFT; Eukaryota.
DR GeneTree; ENSGT00950000182944; -.
DR HOGENOM; CLU_024620_2_1_1; -.
DR InParanoid; Q9Y3R4; -.
DR OMA; FCLLSHD; -.
DR OrthoDB; 652179at2759; -.
DR PhylomeDB; Q9Y3R4; -.
DR TreeFam; TF331063; -.
DR BRENDA; 3.2.1.18; 2681.
DR PathwayCommons; Q9Y3R4; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR Reactome; R-HSA-4085001; Sialic acid metabolism.
DR SABIO-RK; Q9Y3R4; -.
DR SignaLink; Q9Y3R4; -.
DR BioGRID-ORCS; 4759; 6 hits in 1069 CRISPR screens.
DR EvolutionaryTrace; Q9Y3R4; -.
DR GeneWiki; NEU2; -.
DR GenomeRNAi; 4759; -.
DR Pharos; Q9Y3R4; Tbio.
DR PRO; PR:Q9Y3R4; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9Y3R4; protein.
DR Bgee; ENSG00000115488; Expressed in skin of leg and 6 other tissues.
DR Genevisible; Q9Y3R4; HS.
DR GO; GO:1902494; C:catalytic complex; IDA:CAFA.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0052794; F:exo-alpha-(2->3)-sialidase activity; IDA:UniProtKB.
DR GO; GO:0052795; F:exo-alpha-(2->6)-sialidase activity; IEA:UniProtKB-EC.
DR GO; GO:0052796; F:exo-alpha-(2->8)-sialidase activity; IDA:UniProtKB.
DR GO; GO:0004308; F:exo-alpha-sialidase activity; IDA:CAFA.
DR GO; GO:0051692; P:cellular oligosaccharide catabolic process; IDA:CAFA.
DR GO; GO:0006689; P:ganglioside catabolic process; IDA:UniProtKB.
DR GO; GO:0006516; P:glycoprotein catabolic process; IDA:UniProtKB.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; TAS:Reactome.
DR GO; GO:0009313; P:oligosaccharide catabolic process; IDA:UniProtKB.
DR InterPro; IPR011040; Sialidase.
DR InterPro; IPR026945; Sialidase-2.
DR InterPro; IPR026856; Sialidase_fam.
DR InterPro; IPR036278; Sialidase_sf.
DR PANTHER; PTHR10628; PTHR10628; 1.
DR PANTHER; PTHR10628:SF6; PTHR10628:SF6; 1.
DR Pfam; PF13088; BNR_2; 1.
DR SUPFAM; SSF50939; SSF50939; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carbohydrate metabolism; Cytoplasm; Glycosidase; Hydrolase;
KW Lipid degradation; Lipid metabolism; Reference proteome; Repeat.
FT CHAIN 1..380
FT /note="Sialidase-2"
FT /id="PRO_0000208899"
FT REPEAT 127..138
FT /note="BNR 1"
FT REPEAT 197..208
FT /note="BNR 2"
FT MOTIF 20..23
FT /note="FRIP motif"
FT ACT_SITE 46
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:22228546"
FT ACT_SITE 334
FT /note="Nucleophile"
FT ACT_SITE 355
FT /evidence="ECO:0000255"
FT BINDING 21
FT /ligand="substrate"
FT BINDING 41
FT /ligand="substrate"
FT BINDING 179
FT /ligand="substrate"
FT BINDING 181
FT /ligand="substrate"
FT BINDING 218
FT /ligand="substrate"
FT BINDING 237
FT /ligand="substrate"
FT BINDING 304
FT /ligand="substrate"
FT VARIANT 11
FT /note="S -> R (in dbSNP:rs2233384)"
FT /id="VAR_024461"
FT VARIANT 41
FT /note="R -> Q (reduced activity; increased sensitivity to
FT inhibition by oseltamivir carboxylate; dbSNP:rs2233385)"
FT /evidence="ECO:0000269|PubMed:17426694"
FT /id="VAR_024462"
FT VARIANT 145
FT /note="A -> T (in dbSNP:rs2233390)"
FT /id="VAR_049204"
FT VARIANT 168
FT /note="H -> N (in dbSNP:rs2233391)"
FT /evidence="ECO:0000269|PubMed:10191093,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_055311"
FT VARIANT 182
FT /note="R -> Q (in dbSNP:rs2233393)"
FT /id="VAR_055312"
FT MUTAGEN 46
FT /note="D->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:22228546"
FT MUTAGEN 218
FT /note="E->A,Q: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:22228546"
FT MUTAGEN 270
FT /note="Q->E: No effect on enzyme activity."
FT /evidence="ECO:0000269|PubMed:22228546"
FT STRAND 7..14
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:2F0Z"
FT STRAND 20..28
FT /evidence="ECO:0007829|PDB:1SO7"
FT TURN 29..32
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 33..40
FT /evidence="ECO:0007829|PDB:1SO7"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:2F25"
FT STRAND 51..60
FT /evidence="ECO:0007829|PDB:1SO7"
FT TURN 61..64
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:2F10"
FT STRAND 82..91
FT /evidence="ECO:0007829|PDB:1SO7"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 98..108
FT /evidence="ECO:0007829|PDB:1SO7"
FT HELIX 111..115
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:2F12"
FT STRAND 123..131
FT /evidence="ECO:0007829|PDB:1SO7"
FT HELIX 143..147
FT /evidence="ECO:0007829|PDB:1SO7"
FT HELIX 148..153
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 154..159
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 174..182
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 185..188
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 191..201
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 213..225
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 230..250
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 259..265
FT /evidence="ECO:0007829|PDB:1SO7"
FT TURN 268..270
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 275..280
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 290..298
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 301..314
FT /evidence="ECO:0007829|PDB:1SO7"
FT HELIX 318..320
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 325..342
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 346..356
FT /evidence="ECO:0007829|PDB:1SO7"
FT TURN 357..360
FT /evidence="ECO:0007829|PDB:1SO7"
FT STRAND 361..368
FT /evidence="ECO:0007829|PDB:1SO7"
FT HELIX 369..372
FT /evidence="ECO:0007829|PDB:1SO7"
FT HELIX 374..376
FT /evidence="ECO:0007829|PDB:1SO7"
SQ SEQUENCE 380 AA; 42254 MW; AD7B08C478F4D0D9 CRC64;
MASLPVLQKE SVFQSGAHAY RIPALLYLPG QQSLLAFAEQ RASKKDEHAE LIVLRRGDYD
APTHQVQWQA QEVVAQARLD GHRSMNPCPL YDAQTGTLFL FFIAIPGQVT EQQQLQTRAN
VTRLCQVTST DHGRTWSSPR DLTDAAIGPA YREWSTFAVG PGHCLQLHDR ARSLVVPAYA
YRKLHPIQRP IPSAFCFLSH DHGRTWARGH FVAQDTLECQ VAEVETGEQR VVTLNARSHL
RARVQAQSTN DGLDFQESQL VKKLVEPPPQ GCQGSVISFP SPRSGPGSPA QWLLYTHPTH
SWQRADLGAY LNPRPPAPEA WSEPVLLAKG SCAYSDLQSM GTGPDGSPLF GCLYEANDYE
EIVFLMFTLK QAFPAEYLPQ
